title: Topoisomerase 2β: a promising molecular target for primary prevention of anthracycline-induced cardiotoxicity.
abstract: Anthracyclines are powerful chemotherapy agents that are still widely used today. However, their clinical use is limited by the development of dose-dependent cardiotoxicity. Recently, we showed that topoisomerase 2β (Top2β) is required for anthracycline to induce DNA double-strand breaks and changes in the transcriptome, leading to mitochondrial dysfunction and generation of reactive oxygen species. Furthermore, deleting Top2β from cardiomyocytes prevented the development of anthracycline-induced cardiotoxicity in mice. On the basis of this molecular insight, new strategies should be developed to prevent anthracycline-induced cardiotoxicity. First, Top2α-specific anthracyclines should be tested to determine whether they will spare the heart. Second, Top2β should be studied as a potential biomarker to predict risk of developing cardiotoxicity before anthracycline treatment. Third, inhibiting and deleting Top2β in the heart should also be tested as primary prevention strategies. We propose that Top2β is a promising molecular target that can be used to design interventions to prevent anthracycline-induced cardiotoxicity.
authors.affiliation: Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: P
authors.initials: P
authors.lastname: Vejpongsa
authors.affiliation: 1] Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA [2] Texas Heart Institute/St. Luke's Episcopal Hospital, Houston, Texas, USA.
authors.forename: E T H
authors.initials: ET
authors.lastname: Yeh
mesh_terms: D000818:Animals; D018943:Anthracyclines / Q000037:antagonists & inhibitors / Q000633:toxicity*; D054715:Cardiotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology; D011322:Primary Prevention / Q000379:methods*
chemical_list: D018943:Anthracyclines; D054715:Cardiotoxins; D004268:DNA-Binding Proteins; D004250:DNA Topoisomerases, Type II